The active ingredient of the aqueous suspension obtainable by the method of the invention, namely 5-(3-ethoxy-4-n-pentyloxyphenyl)thiazolidine-2,4-dione (hereinafter sometimes referred to briefly as CT-112), is a known compound having aldose reductase inhibitory activity. It has been demonstrated that this compound exerts prophylactic and therapeutic effects on chronic symptoms of diabetic cataract, neuropathy and retinopathy in mammals inclusive of man (Japanese Kokai Patent Application No. 57-28075) and therapeutic efficacy in diseases of the iris and cilia (Japanese Kokai Patent Application No. 61-43114).
When an aqueous preparation of CT-112, such as eyedrops or an injection, is to be manufactured for the treatment or prevention of the above-mentioned diseases, it is necessary to suspend the compound in water because CT-112 is only sparingly soluble in water over the pH range which is acceptable for a topical drug or an injection.
However, if such an aqueous suspension is prepared by the conventional pharmaceutical procedure, for example by dispersing the bulk powder of CT-112 directly in water or dissolving it in an appropriate solvent and, then, processing the solution into an aqueous suspension, the resulting aggregation of CT-112 or entrapment thereof in foams in the course of manufacture or adsorption of CT-112 on the container wall will lead to decreases in content and poor dispersion, thus making it extremely difficult to provide a stable aqueous CT-112 suspension.
Accordingly the inventors of the present invention explored into this field of technology for overcoming the above-mentioned drawbacks and found surprisingly that a stable aqueous suspension free from the above disadvantages can be successfully prepared by providing an aqueous solution of CT-112 whose pH has been previously adjusted to a certain value and then adjusting the pH of said aqueous solution in the presence of a defined water-soluble macromolecular compound.